crossing96/oncoscreening huggingface dataset:
Intradermal priming to intravesical Bacillus Calmette-Guérin in non-muscle invasive bladder cancer: A translational research and phase I clinical trial.	OBJECTIVE: To determine the safety and the role of modulating cytokines and proteases in the immune response to intravesical Bacillus Calmette-Guérin (BCG) when primed with systemic intradermal BCG. METHODS: Phase 1 and mechanistic longitudinal, prospective, single-blind randomized study (NCT04806178). Twenty-one non-muscle invasive urothelial bladder cancer patients undergoing intravesical adjuvant BCG after transurethral resection of bladder tumor (TURBT) in a teaching hospital between September 2021 and April 2023 were randomized to 0.1 mL of intradermal BCG vaccine or placebo (0.9% saline) administered 15 days before the start of intravesical BCG therapy. Blood samples were evaluated mechanistically regarding eight cytokines serum levels interferon-induced transmembrane protein 3 Gene (IFITM3), Interleukin 1 beta (IL1-BETA), interleukin-2 receptor alpha chain (IL2 RA), Interleukin 6 (IL 6), Interleukin 10 (IL 10), Tumor necrosis factor alpha (TNF-α), Interferon-β, AXL, and one protease CASPASE 8. RESULTS: After 1 exclusion, twenty patients were randomized to intradermal BCG (n = 11) and intradermal placebo (n = 9). There was no difference in adverse effects emerging from the intravesical Onco-BCG therapy, and no difference in the expression of the cytokines and proteases analyzed between control and intervention, and over time. CONCLUSIONS: Intradermal BCG administration before intravesical application was safe, with no increase in adverse effects. It also does not seem to change the analyzed targets during the intravesical induction-phase BCG. Other immune targets should be explored in the future. The Brazilian tuberculosis-endemic status, where BCG vaccination is mandatory, might have affected the results.	bladder
Sex-based differences in genetic alterations and immune checkpoint inhibitor response in urothelial bladder cancer.	INTRODUCTION: Bladder cancer exhibits significant sex-based disparities, with men showing higher incidence rates and women experiencing more aggressive disease and poorer survival outcomes. This study investigates sex-specific somatic genetic alterations (GAs) in urothelial bladder cancer and their effects on survival, immune cell infiltration, and immune checkpoint inhibitor (ICI) responses. METHODS: We analyzed 3,157 patients with urothelial bladder cancer using next-generation sequencing data from the American Association for Cancer Research (AACR) Project GENIE. Kaplan-Meier analysis assessed overall survival, while TIMER2.0 and ROC Plotter evaluated immune cell infiltration and ICI responses. Synthetic lethal interactions were identified through the SLOAD database, and co-occurrence patterns were examined (significance at P < 0.05). RESULTS: Among the 3,157 patients (median age: 70), 76% were male. Somatic gene alterations were identified in 35% of cases, more frequently in men (38% vs. 29%, P < 0.001). Men had more alterations in RB1, CDKN1A, and ERCC2 (all P < 0.001), while AR gene alterations were more common in women. Patients with CDKN1A, RB1, or ERCC2 alterations had significantly worse 5-year survival (18-27 vs. 35.4 months; P = 0.0219), with RB1 alterations linked to the lowest 10-year survival rates (21.3% vs. 28.3%, P = 0.0219). Immune profiling revealed increased CD8⁺ T cell and NK cell infiltration in RB1-altered tumors, while AR alterations correlated with decreased monocyte infiltration. CONCLUSION: Somatic GAs contribute to sex-based survival disparities in bladder cancer. RB1 and AR alterations emerge as critical drivers of poor outcomes and potential therapeutic targets, underscoring the need for sex-tailored treatment strategies.	bladder
Bladder cancer risk in aluminum production workers: A systematic review.	OBJECTIVE: To summarize the key findings of occupational exposures during aluminum production in cohort studies on bladder cancer published between 1979 and 2023. MATERIALS AND METHODS: This systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO. Study quality was evaluated using the Newcastle-Ottawa scale. RESULTS: The literature search identified 24 cohort studies examining the standardized incidence (SIR) and mortality ratios (SMR) of bladder cancer among aluminum production workers. Five of the 13 studies examined SIR (95% CI) and three of the 16 studies that examined SMR (95% CI) reported a statistically significant increased risk of bladder cancer among aluminum production workers. The highest SIR was recorded in the secondary aluminum smelter (2.85; 95% CI: 1.23-5.62), suggesting a significantly elevated risk. In aluminum reduction plants, the SIR was 1.82 (95% CI: 1.59-2.07), while in Söderberg plants, it was 1.69 (95% CI: 1.06-2.57) and 1.4 (95% CI: 1.0-1.9), respectively. For aluminum plants overall, the SIR was 1.30 (95% CI: 1.10-1.50). The results indicate an increased risk, with the highest SMR of 5.90 (95% CI: 1.58-15.1), suggesting a significantly elevated hazard in the secondary aluminum smelter. The other values-3.47 (95% CI: 1.25-9.62) for the aluminum smelter and 2.24 (95% CI: 1.77-2.79) for the aluminum reduction plant-also indicate an increased risk, albeit with varying degrees of statistical certainty. CONCLUSION: The International Agency for Research on Cancer has classified aluminum production as a Group 1 carcinogenic activity, providing strong evidence of its association with bladder cancer. The studies primarily included workers from Prebake, Söderberg, and aluminum reduction plants. Some findings indicate a significant yet variable risk across different segments of aluminum production. However, the review did not clearly confirm an increased risk of bladder cancer in specific aluminum-related occupations. Aluminum exposure may influence the lifetime risk of bladder cancer among these workers.	bladder
[A Case of Cut-to-the-light Incision for Ureteroileal Anastomotic Obstruction after Robot-Assisted Radical Cystectomy and Ileal Conduit].	A 68-year-old man with muscle invasive bladder cancer underwent robot-assisted radical cystectomy and ileal conduit for urinary diversion using the Wallace procedure. Two months after surgery, the patient developed recurrent urinary tract infections, and computed tomography showed left hydronephrosis. Nephrostography revealed a left ureteroileal anastomotic obstruction. Ho-YAG laser-assisted incision and transureter dilatation were performed 6 months after surgery. Nephrostography performed 1 month after dilatation confirmed improvement of the obstructed area and no symptom recurrence.	bladder
Avelumab First-line Maintenance for Advanced Urothelial Carcinoma: Long-term Outcomes from the JAVELIN Bladder 100 Trial in Patients with Nonvisceral or Lymph Node-only Disease.	In the JAVELIN Bladder 100 randomized phase 3 trial (N = 700), avelumab first-line maintenance plus best supportive care (BSC) significantly prolonged overall survival (OS; primary endpoint) and progression-free survival (PFS) versus BSC alone in patients with advanced urothelial carcinoma (aUC) without progression after first-line platinum-based chemotherapy (PBC). Here, we report exploratory analyses of subgroups with nonvisceral metastases at the start of PBC (including bone metastases) or lymph node-only disease at randomization. The median OS with avelumab versus control in patients with nonvisceral metastases (n = 318) was 31.4 versus 17.1 mo (hazard ratio [HR], 0.60 [95% confidence interval {CI}, 0.45-0.79]), and in patients with lymph node-only disease (n = 102), it was 31.9 versus 22.7 mo (HR, 0.86 [95% CI, 0.51-1.47]). In patients with nonvisceral metastases, prolonged OS was observed with avelumab irrespective of the response to PBC or PBC regimen received. PFS analyses favored avelumab over control in all the subgroups. Incidences of avelumab-related adverse events were similar across the subgroups. Limitations include small sample sizes and the exploratory nature of analyses. Overall, exploratory analyses suggest that in first-line PBC-treated patients without progression, avelumab maintenance is effective and has a manageable toxicity profile in patients with aUC who have nonvisceral metastases or lymph node-only disease.	bladder
Avelumab plus sacituzumab govitecan versus avelumab monotherapy as first-line maintenance treatment in patients with advanced urothelial carcinoma: JAVELIN Bladder Medley interim analysis.	BACKGROUND: Avelumab first-line maintenance is a recommended treatment option for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) without progression following platinum-based chemotherapy (PBC). The JAVELIN Bladder Medley phase II trial is investigating the efficacy and safety of maintenance treatment with avelumab combined with other antitumor agents versus avelumab monotherapy. We report an interim analysis of avelumab plus sacituzumab govitecan (SG) versus avelumab monotherapy. PATIENTS AND METHODS: Patients with la/mUC without progression after first-line PBC were randomized 2 : 1 to receive avelumab (800 mg every 2 weeks) plus SG (10 mg/kg on days 1 and 8 of 21-day cycles) or avelumab monotherapy (800 mg every 2 weeks). Primary endpoints are investigator-assessed progression-free survival (PFS) and safety. For PFS and overall survival (OS), data in the avelumab monotherapy arm were extended per protocol using propensity score-weighted JAVELIN Bladder 100 data. RESULTS: At data cut-off (16 September 2024), 38/74 patients (51.4%) in the avelumab plus SG arm and 10/37 patients (27.0%) in the avelumab monotherapy arm were still receiving study treatment. Median PFS with avelumab plus SG versus avelumab monotherapy was 11.17 versus 3.75 months, respectively [hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.31-0.76; prespecified efficacy boundary: HR ≤ 0.60]. OS data were immature; median OS was not reached versus 23.75 months, respectively (HR 0.79, 95% CI 0.42-1.50). In patients treated with avelumab plus SG or avelumab monotherapy, any-grade treatment-related adverse events (TRAEs) occurred in 97.3% versus 63.9% (grade ≥3 in 69.9% versus 0%), respectively. CONCLUSION: In patients with la/mUC without progression after first-line PBC, PFS was prolonged with avelumab plus SG versus avelumab monotherapy as maintenance treatment. TRAEs were more frequent with the combination and were consistent with known safety profiles of SG and avelumab. Combining avelumab with anti-Trop-2 antibody-drug conjugates may be a promising strategy to improve patient outcomes in la/mUC.	bladder
When A Health Economist Becomes A Cancer Patient.	A health economist offers a glimpse into his own health care decision making when he is diagnosed with bladder cancer.	bladder
Global Trends in the Incidence, Mortality, and Risk-attributable Deaths for Prostate, Bladder, and Kidney Cancers: A Systematic Analysis from the Global Burden of Disease Study 2021.	BACKGROUND AND OBJECTIVE: Bladder cancer (BCa), kidney cancer (renal cell carcinoma [RCC]), and prostate cancer (PCa) altogether contribute remarkably to global cancer morbidity and mortality. However, comprehensive global assessments of their incidence and mortality trends are lacking. This study aimed to assess the global, regional, and national burden of the urological cancers using the most updated data from the Global Burden of Disease (GBD) 2021 study. METHODS: Data on these urological cancers were extracted from the GBD 2021 database. Age-standardized incidence rates (ASIRs) and age-standardized death rates (ASDRs) were calculated by sex, region, and sociodemographic index (SDI). KEY FINDINGS AND LIMITATIONS: In 2021, there were 2.25 million new cases and 815 546 deaths from urological cancers globally. PCa had the highest incidence and mortality burden, followed by BCa and RCC. From 2000 to 2021, ASIR increased for RCC (average annual percent change [AAPC]: 0.15%, 95% confidence interval [CI] 0.07-0.23%), while it declined for BCa (AAPC: -0.48%, 95% CI -0.54% to -0.43%) and PCa (AAPC: -0.12%, 95% CI -0.24% to -0.01%). ASDRs decreased for all three cancers, with BCa showing the largest reduction (AAPC: -1.02%, 95% CI -1.08 to -0.97%). The incidences were higher in high- to middle-SDI regions. Smoking and a high body mass index were the leading causes of risk-attributable deaths of urological cancers. CONCLUSIONS AND CLINICAL IMPLICATIONS: The GBD 2021 study revealed that the incidences and mortality burden of these urological cancers remained significant. Public health strategies targeting early detection and modifiable risk factors are crucial to further reduce the evolving burden of these cancers.	bladder
Risk assessment for the bladder carcinogenesis of 4-aminobiphenyl in smokers: A source-to-outcome study.	4-aminobiphenyl (4-ABP) is widely distributed in the environment and is implicated in the pathogenesis of cancer. This study aims to clarify the environmental and toxicological science of 4-ABP, which are currently unexplored. By searching articles from PubMed, Web of Science, and MEDLINE, we established an aggregate exposure pathway (AEP) framework that demonstrated the presence of 4-ABP in the cigarette smoke. Compared to nonsmokers, smokers had relatively higher levels of 4-ABP and its adducts in blood, urine, and bladder tissues. Then, an adverse outcome pathway (AOP) was constructed using bioinformatic tools. The AOP indicated that 4-ABP induced DNA damage, cell cycle dysregulation, and angiogenesis in the development of bladder cancer. In vitro assays confirmed that 4-ABP/cigarette smoke extract (CSE) significantly induced DNA double strand breaks and cell cycle arrest in the S phase in bladder cancer cells (J82), and 4-ABP/CSE-treated J82 cells promoted the migration and tube formation ability of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. The benchmark dose (BMD) analysis revealed that the 5th lower limit of BMD at a 5 % response (BMDL(5)) derived from angiogenesis was 0.02 mM, and the corresponding human equivalent dose derived from BMDL(5) was 0.44 μg/kg/day. Our study demonstrated that 4-ABP induced bladder cancer via promoting angiogenesis in smokers, which may provide a new approach for chemical risk assessment regarding bladder carcinogenesis.	bladder
The Effect of Surgeon Experience on the Recurrence of Non-Muscle Invasive Bladder Cancer (NMIBC), Following Transurethral Resection of the Bladder Tumor (TURBT): A double Blinded Prospective Randomized Study.	BACKGROUND: Transurethral resection of the bladder tumor (TURBT) followed by intravesical instillation therapy is the standard treatment for non-muscle invasive bladder cancer (NMIBC). One of the factors that may affect the risk of recurrence after TURBT is the quality of surgery that may vary between individual surgeons. While there has been a large number of studies demonstrating the ability to reduce the risk of recurrence of NMIBC with different types of the intravesical therapy, less attention was paid to the quality of TURBT in improving long-term treatment results. The aim of the study is to evaluate the effect of the quality of TURBT on the recurrence rate of NMIBC based on surgeon experience. METHODS: The study is a double blinded prospective randomized study conducted on 50 patients with NMIBC. who underwent 126 procedures (50 primary cystoscopies ,26 restaging cystoscopies and 50 check cystoscopies at three months). All Treatment-naive patients with NMIBC candidate for TURBT were included, with exclusion of patients with previous history of TURBT, previous open bladder surgery, patients with urethral stricture, patients with muscle invasive bladder cancer. And patients who lost follow up. Patients were randomized by closed envelope into two groups; Group A included 25 patients who underwent TURBT by a senior surgeon (more than 5 years' experience), and Group B included 25 patients underwent TURBT by a qualified junior surgeon (less than 5 years' experience).  Restaging cystoscopy at 2-6 weeks (if indicated) and follow up cystoscopy at three months were performed by another senior surgeon (who was blinded to the name of the first surgeon). RESULTS: No statistically significant difference was found between both groups regarding the incidence of complications (urethral injury, bladder perforation, ureteric injury, obturator reflex), Group B showed a statistically significant longer operative time, postoperative irrigation time, more hemoglobin loss, longer hospital stay, and higher 3 months' recurrence rates. Moreover, senior surgeons' specimens were more likely to include detrusor muscles. CONCLUSION: surgeon's experience has significant impact on the quality of TURBT and risk of recurrence of NMIBC. With less operative time, less hemoglobin drop, and less hospital stay.	bladder
A lactate-related tSNE signature defines prognostic subtypes of bladder cancer and reveals LINC01094-mediated VIM stabilization in metastasis and drug resistance.	BACKGROUND: Bladder cancer (BLCA) is prone to metastasis and often shows poor responses to chemotherapy and immunotherapy. Investigating the underlying mechanisms of metastasis and drug resistance may therefore offer new therapeutic strategies for BLCA. METHODS: Publicly available datasets were analyzed using consensus clustering and t-distributed stochastic neighbor embedding (tSNE) to characterize a lactate-related gene signature in BLCA. Gene set variation analysis (GSVA) was employed to assess signaling pathway activity, while immune cell infiltration in the tumor microenvironment (TME) was evaluated using single-sample gene set enrichment analysis (ssGSEA), the Estimation of Stromal and Immune cells in Malignant Tumors using Expression data (ESTIMATE), and CIBERSORT. RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays were then performed to confirm molecular interactions. RESULTS: Two distinct BLCA subtypes were identified based on lactate-related gene expression, and a lactate-based tSNE score was constructed. This score demonstrated prognostic value and was integrated into a nomogram confirmed by a calibration curve. Functionally, higher tSNE scores correlated with immune- and inflammation-related pathways, as well as with immunotherapy efficacy in BLCA. Among candidate regulators identified, LINC01094 emerged as a key factor in BLCA metastasis and drug resistance. LINC01094 was predominantly localized in the cytoplasm and was upregulated in tumor tissues compared with adjacent normal tissues, acting as an unfavorable prognostic factor. In vitro, LINC01094 promoted metastasis and chemotherapy resistance, potentially by stabilizing VIM protein levels and inhibiting its ubiquitination. CONCLUSIONS: This comprehensive analysis of lactate-related genes reveals how this gene signature may shape the tumor microenvironment and affect BLCA patient prognosis. Additionally, our data suggest that targeting LINC01094 with antisense oligonucleotides (ASOs) could reduce BLCA cell metastasis and enhance their sensitivity to chemotherapy.	bladder
Associations of a claims-based frailty index with perioperative outcomes and survival among older adults undergoing radical cystectomy for bladder cancer.	OBJECTIVE: Frailty is increasingly recognized as an important component of geriatric assessment in older adults and an important predictor of clinical outcomes. Bladder cancer (BC) is a potentially lethal disease, and treatments like radical cystectomy (RC) are associated with high rates of morbidity. We examined the associations of baseline frailty with perioperative outcomes and survival in a population-based cohort of older adults undergoing RC. MATERIALS AND METHODS: We identified older adults aged 66 to 89 years with Tany Nany cM0 urothelial carcinoma of the bladder who underwent RC from 2000 to 2017 in SEER-Medicare. Baseline frailty was assessed using the claims-based frailty index (CFI), a validated deficit accumulation frailty measure, within the 12-months preceding surgery. The associations of CFI with perioperative outcomes and survival were evaluated using multivariable regression models. RESULTS: A total of 6,041 patients were included in the study cohort, including 2,640 (44%) who were robust (CFI <0.15), 2,980 (49%) who were prefrail (CFI 0.15-<0.25), and 421 (7%) who were mildly to severely frail (CFI ≥0.25). Increasing CFI was associated with statistically significantly higher rates of prolonged hospitalization, 90-day emergency department utilization, 90-day complications, and 90-day hospital readmission, and fewer healthy days at home (HDAH). CFI remained independently associated with an increased risk of perioperative outcomes and worse mortality in multivariable regression models. CONCLUSIONS: In a national, contemporary cohort of older adults with BC undergoing RC, increasing frailty was independently associated with a higher risk of perioperative morbidity, fewer HDAH, and worse mortality. The CFI provides an objective assessment to improve decision-making in older adults with bladder cancer.	bladder
Recurrence risk prediction for non-muscle-invasive bladder urothelial carcinoma using diffusion and clinicopathology features.	PURPOSE: To investigate the prognostic value of apparent diffusion coefficient (ADC) metrics, MRI characteristics, and clinicopathological parameters in predicting non-muscle-invasive bladder urothelial carcinoma (UCB) recurrence, and to develop a novel multiparametric risk stratification framework. METHODS: This retrospective single-center study (n = 135) with histologically confirmed non-muscle-invasive UCB diagnosed between January 2015 and March 2023. ADC values, vesical imaging reporting and data system (VI-RADS) scores, and clinicopathological variables were analyzed with recurrence-free survival (RFS) as the primary endpoint. Prognostic determinants were identified using univariate and multivariate Cox proportional hazard regression models. An advanced risk stratification system was developed using independent predictors and validated against the European Association of Urology (EAU) risk classification using concordance index (C-index). RESULTS: Multivariate analysis identified three independent predictors: ADC values (HR = 0.104, 95% confidence interval (CI) 0.025-0.436), hemoglobin levels (HR = 0.463, 95% CI 0.223-0.960), and pathological grade (HR = 2.079, 95% CI 1.098-3.936). The combined model incorporating these parameters demonstrated moderate predictive accuracy (C-index = 0.724, 95% CI 0.655-0.794). Notably, VI-RADS scores showed no independent prognostic value. Risk stratification based on ADC (≤ 1343.22 × 10⁻⁶ mm²/s), hemoglobin (< 113.2 g/L), and pathological grade demonstrated superior discriminative capacity compared to EAU criteria (C-index: 0.667 vs. 0.605). CONCLUSION: A multidimensional prognostic framework integrating quantitative ADC metrics, hemoglobin levels, and pathological grading significantly outperforms conventional EAU stratification in predicting non-muscle-invasive UCB recurrence, providing clinically actionable thresholds for personalized risk stratification and UCB management.	bladder